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Crystal Engineering for inhaled delivery
The IPI CIC has access to a range of crystal engineering processing expertise and technologies for manufacturing particles with suitable characteristics for inhalation, these include particle size reduction technologies such as micronisation and nano-milling/spray drying, which enables preparation of porous spherical particles. In addition we can use supercritical fluid technology to prepare, with controlled precision, particles with optimised morphology and surface characteristics.
Inhalation is the most effective route of drug administration for treating diseases of the respiratory tract. This route ensures that drugs are delivered directly to their site of action where they exert the required local effect. The three main inhalation approaches include the use of metered dose inhalers (MDIs), dry powder inhalers (DPIs) and nebulisers.
The IPI CIC offer a range of services for preclinical inhaled delivery development including development and testing of DPI and nebulised formulations.
DPI Formulation development and testing
The DPI is rapidly becoming popular as it reduces issues of coordination and high plume velocity without requiring large spacers or holding chambers. However, nebulisers have the advantage of delivering drugs during normal tidal breathing so are useful during acute exacerbations. They do not require a controlled inhalation manoeuvre, high levels of co-ordination, or large inspiratory flows.
The Next Generation Impactor will be used to measure aerodynamic particle size distribution of the DPI formulation(s). This system has a number of stages simulating the various parts of the human respiratory system. The particle stream passes through a number of stages in series at a constant air flow. Particles with specific size and thus inertia will impact upon specific stages of the impactor allowing fractionation and classification of aerodynamic particle size distribution. Particles having aerodynamic diameter less than 6µm typically demonstrate potential to deposit in the human respiratory tract. By analysing the amount of drug deposited on the various stages an estimation of fine particle dose and the proportion of the emitted doses with potential for lung deposition can be calculated.
Our structured approach to DPI formulation development includes:
Phase 1-Micronisation and associated analysis
Phase 2–Blend with lactose
Phase 3-DPI Next Generation Impactor Testing
Phase 4-Stability testing of micronised and blended API
Phase 5-NGI study on stored materials
Nebuliser formulation development and testing
Nebulisation allows fit for purpose formulations to be developed rapidly for use in preclinical and early clinical studies. In exploiting this approach, however, it is necessary to determine the aerosol output from selected nebulisers and assess the associated aerodynamic particle size characteristics of formulations, which will determine the extent of lung deposition in animal models and in man. In this regard, Next Generation Impactor (NGI) and Aerosol Output studies will be undertaken on the candidate drug when formulated in fit for purpose aqueous solutions. Studies are generally performed on a range of nebuliser devices, which will include a standard jet nebuliser system (1) alongside portable ultrasonic (2) and vibrating mesh (3) devices which have the potential to provide more efficient nebulisation and smaller aerodynamic particle size leading to greater lung deposition.
Studies will also be undertaken at a range concentrations starting with 1 mg/ml as standard. Further samples will be tested using the preferred nebuliser device at 1 in 10 and 1 in 100 dilutions to ensure that predictable aerosol output and particle size is achieved across the possible range of concentrations to be used in in-vivo studies.
Our structured approach to Nebulised formulation development includes:
Selection of nebuliser devices for the study
Analytical Method Transfer
Next Generation Impactor Testing
Aerosol Output study
Variation in Concentration study
Solution stability testing
